Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin
- Others:
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)) ; Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
- Institut de Génomique Fonctionnelle (IGF) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- This work was supported by the Centre National de la Recherche Scientifique, a grant from the Société Francophone du Diabète (SFD 2011) to Thierry Coppola and a grant from the Agence Nationale de la Recherche (ANR-13-SAMA-0002) to Jean Mazella. Amar Abderrahmani is supported by "European Genomic Institute for Diabetes" (EGID, ANR-10-LABX-46), European Commission, the Regional Council Nord Pas de Calais and the European Regional Development Fund. Alaeddine Djillani is supported by ICST LabEx.
- ANR-13-SAMA-0002,VASPAC,Validation du concept spadine pour le traitement de la dépression(2013)
- ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010)
- ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011)
Description
Inhibition of the potassium channels TREK-1 by spadin (SPA) is currently thought to be a promising therapeutic target for the treatment of depression. Since these channels are expressed in pancreatic β-cells, we investigated their role in the control of insulin secretion and glucose homeostasis. In this study, we confirmed the expression of TREK-1 channels in the insulin secreting MIN6-B1 β-cell line and in mouse islets. We found that their blockade by SPA potentiated insulin secretion induced by potassium chloride dependent membrane depolarization. Inhibition of TREK-1 by SPA induced a decrease of the resting membrane potential ( mV) and increased the cytosolic calcium concentration. In mice, administration of SPA enhanced the plasma insulin level stimulated by glucose, confirming its secretagogue effect observed in vitro. Taken together, this work identifies SPA as a novel potential pharmacological agent able to control insulin secretion and glucose homeostasis.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-02266863
- URN
- urn:oai:HAL:hal-02266863v1
- Origin repository
- UNICA